The purpose of this application is to request funds to continue the research and training activities of the Washington University Drug Abuse Research Center. In addition to our training activities the following projects represent the specific research goals of the Center: (1) To examine the effects of the narcotics on the hypothalamic-pituitary-gonadal axis. These studies involve a series of in vivo and in vitro experiments designed to evaluate the peripheral and central nervous system factors involved in the adverse effects of the narcotics on reproductive endocrinology in the male rat and human; (2) The goals of this project are to clarify the mechanism and locus of action of the narcotics on the hypothalamus. Specifically, these studies will employ a combination of ultrastructural, pharmacological and immunochemical methods to define the locus of narcotic action to functionally identifiable neuronal elements in the hypothalamus; (3) The purpose of this study will be to explore the possibility that exposure of the developing organs to delta 9 Tetrahydrocannabinol might have adverse effects on the nervous system. A primary focus of this research will be on the ultrastructural changes occurring in the developing hypothalamus; (4) The overall objective of this project is to determine the neurochemical changes which occur in individual hypothalamic nuclei after acute and chronic morphine administration particularly with respect to the processes of tolerance and physical dependence; (5) The long term objective of this project is to define in molecular terms, particularly at the membrane level the mechanisms underlying opiate tolerance, addiction and withdrawal; (6) To determine whether chronic alcoholism is associated with an abnormally high loss of cells, particularly neurons in brain; (7) The overall objective of this project is to investigate the possible relationship between the CNS actions of the three most widely abused CNS depressant and the metabolic state of the aldehyde intermediates of biogenic amine metabolism.